Clostridium difficile infection (CDI) involves a range of clinical presentations including mild to self-limiting diarrhea to life-threatening pseudomembranous colitis and megacolon. Many healthy persons (e.g., infants) carry Clostridium difficile (C. difficile), and many patients become asymptomatic carriers after admission to the hospital. Most cases are diagnosed based on clinical evaluations, history of antibiotic use, and the presence of the organism and/or toxins A & B (i.e., TcdA and TcdB, respectively) in the stool. Enzyme-linked immunoassay (EIA) tests are the most frequently used test format for measuring toxin in the stool specimens, with tissue culture combined with specific neutralization being the gold standard for detecting stool toxin. More recently, polymerase chain reaction (PCR) tests are available for determining the presence of C. difficile toxin A and B genes (tcdA and tcdB) and these are used as standalone tests and in combination with the detection of glutamate dehydrogenase (GDH) for ruling out C. difficile-negative patients. All of these assays are suitable for detecting the presence of C. difficile as an aid to diagnosis but do not provide information about the severity of disease or confirming that C. difficile actually is responsible for symptoms in patients with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), other enteric infections and diarrhea causing agents like laxatives and antibiotics.
The presence and severity of the disease is an important factor for recommending a proper course of treatment. In general, patients with C. difficile disease often present with fever, have slightly raised white blood cells (leukocytosis), and experience mild abdominal pain. Carrier status includes those patients that are colonized with C. difficile but lack stool toxin and intestinal inflammation indicating that something else is causing the symptoms. Patients that are determined to be carriers may still be placed in isolation wards but wouldn't receive treatment for CDI. Determining carrier status is important when deciding on a course of treatment since antibiotics could actually disrupt the normal flora making the patient susceptible to C. difficile disease. In addition, a low level of cells as indicated by low levels of C. difficile GDH may further differentiate between patients that are infectious versus noninfectious and, thus, allowing discharge from isolation wards.
For patients with disease, mild cases respond well to stopping the inciting antibiotic while moderate to severe C. difficile disease cases often require antibiotic intervention. Currently, no single lab parameter is routinely used to stratify patients based on severity of C. difficile-associated disease (CDAD) for optimizing medical and/or surgical treatment. The relapse rate is about 20% of patients occurring within days to a month following the end of antibiotic treatment.